Huaier Extract Attenuates Acute Kidney Injury to Chronic Kidney Disease Transition by Inhibiting Endoplasmic Reticulum Stress and Apoptosis via miR-1271 Upregulation

Biomed Res Int. 2020 Dec 10:2020:9029868. doi: 10.1155/2020/9029868. eCollection 2020.

Abstract

Endoplasmic reticulum stress (ERS) is strongly associated with acute kidney injury (AKI) to chronic kidney disease (CKD) transition. Huaier extract (HE) protects against kidney injury; albeit, the underlying mechanism is unknown. We hypothesized that HE reduces kidney injury by inhibiting ERS. In this study, using an AKI-CKD mouse model of ischemia-reperfusion injury (IRI), we evaluated the effect of HE on AKI-CKD transition. We also explored the underlying molecular mechanisms in this animal model and in the HK-2 human kidney cell line. The results showed that HE treatment improved the renal function, demonstrated by a significant decrease in serum creatinine levels after IRI. HE appreciably reduced the degree of kidney injury and fibrosis and restored the expression of the microRNA miR-1271 after IRI. Furthermore, HE reduced the expression of ERS markers glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) and inhibited apoptosis in the IRI group. This in vivo effect was supported by in vitro results in which HE inhibited apoptosis and decreased the expression of CHOP and GRP78 induced by ERS. We demonstrated that CHOP is a target of miR-1271. In conclusion, HE reduces kidney injury, probably by inhibiting apoptosis and decreasing the expression of GRP78 and CHOP via miR-1271 upregulation.

MeSH terms

  • Acute Kidney Injury / drug therapy*
  • Animals
  • Apoptosis*
  • Cell Line
  • Complex Mixtures / pharmacology*
  • Disease Progression
  • Endoplasmic Reticulum Chaperone BiP
  • Endoplasmic Reticulum Stress*
  • Gene Expression Regulation*
  • Heat-Shock Proteins / biosynthesis
  • Humans
  • Kidney Failure, Chronic / drug therapy*
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Trametes
  • Transcription Factor CHOP / biosynthesis
  • Up-Regulation*

Substances

  • Complex Mixtures
  • DDIT3 protein, human
  • Ddit3 protein, mouse
  • Endoplasmic Reticulum Chaperone BiP
  • HSPA5 protein, human
  • Heat-Shock Proteins
  • Hspa5 protein, mouse
  • MIRN1271 microRNA, human
  • MicroRNAs
  • huaier
  • Transcription Factor CHOP